Xenopus paraxial protocadherin has signaling functions and is involved in tissue separation

Abstract

Protocadherins have homophilic adhesion properties and mediate selective cell–cell adhesion and cell sorting. Knockdown of paraxial protocadherin (PAPC) function in the Xenopus embryo impairs tissue separation, a process that regulates separation of cells of ectodermal and mesodermal origin during gastrulation. We show that PAPC can modulate the activity of the Rho GTPase and c-jun N-terminal kinase, two regulators of the cytoskeletal architecture and effectors of the planar cell polarity pathway. This novel signaling function of PAPC is essential for the regulation of tissue separation. In addition, PAPC can interact with the Xenopus Frizzled 7 receptor, and both proteins contribute to the development of separation behavior by activating Rho and protein kinase Cα

A methylome-wide study of aging using massively parallel sequencing of the methyl-CpG-enriched genomic fraction from blood in over 700 subjects

“…Methylation has been shown to regulate expression of the different isoforms encoded by the cluster (53). Protocadherins have been shown to interact with c-Jun N-terminal kinases (JNKs) and frizzled 7 in model organisms (54). The former was the top protein -protein interaction network finding in our results, and the latter was among the top aging loci identified by Salpea et al (34).…”

PCDH8, the human homolog of PAPC, is a candidate tumor suppressor of breast cancer

“…It will be interesting to dissect the intracellular signals that PCDH8 regulates in breast epithelial cells. Inactivating PCDH8 appears to be an early step in breast tumor progression that may be related to its role in regulating cellular polarity and tissue organization during vertebrate embryogenesis (Hukriede et al, 2003;Medina et al, 2004;Unterseher et al, 2004). Given its high frequency of inactivation, it is likely to represent a key step in the evolution of breast epithelial malignancy.…”

Secreted Frizzled-related Protein 2 (sFRP2) Redirects Non-canonical Wnt Signaling from Fz7 to Ror2 during Vertebrate Gastrulation

“…All experiments complied with local (Regierungspräsidium Karlsruhe, Az.35-9185.82) and international guidelines for the use of experimental animals. Embryos were essentially obtained by in vitro fertilization, microinjected, and cultured as described previously (32). The injection sites, construct compositions, and stages used in the individual experiments are indicated in the figure legends and in the following sections.…”